Cephalosporins obtained by fermentation processes or ring expansion of penicillins all contain the 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene nucleus, i.e. ##STR1## Compounds with this ring system have been the object of intense research and numerous scientific articles and patents. As a result of this effect, approximately eight commercial products are available today as antibacterial agents.
Analogous rings systems in which the sulfur atom has been moved to another position in the six-membered ring can not be obtained by the same methods as described for the above nucleus. A totally synthetic approach to this ring system must be employed. One system which has been attempted with varied success is the 8-oxo-4-thia-1-azabicyclo[4.2.0]octane for which the trival name isocephalosporin can be given, i.e. ##STR2##
The synthesis of 7.beta.-phenylacetamido-7.alpha.-methyl-6.alpha.H-8-oxo-4-thia-1-azabicycl o[4.2.0]oct-2-ene-2-carboxylic acid and the 2,3-dihydro derivative has been reported in J. Chem. Soc. 1321 (1973). These compounds lack the 2-3 double bond believed necessary for biological activity and/or have a 7.alpha.-methyl group which is not present in naturally occurring cephalosporins. These two compounds were reported to have no antibacterial activity when tested at high levels against three bacteria. Also reported within this reference was a derivative with transconfiguration, 7.alpha.-phenylacetamido-6.alpha.H-8-oxo-4-thia-1-aza[4.2.0]octane-2-carbo xylic acid. This compound also showed no activity. Within this reference attempts to prepare the nucleus without the methyl substituent and with the 2-3 double bond were unsuccessful. Further attempts were reported in J. Chem. Soc. Perkin I, 2092 (1974) and were also unsuccessful.
We have now prepared the 6,7.alpha.H-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene ring system; in particular, 7.beta.-acylamino-6.alpha.H-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-ca rboxylic acids and derivatives thereof.